• Bilateral Thigh Muscle Area and Volume by CT scan [ Time Frame: baseline and 3 months (post intervention) ] [ Designated as safety issue: No ]
  

• Bilateral Thigh Intramuscular Fat by CT [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Histochemical analyses of fiber type and capillary density fom Bilateral Thigh Muscle Biopsy samples [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Muscle Fiber proportion and mean cross sectional area by immunohistochemistry [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Myosin Heavy Chain Isoform expression by gel electrophoresis [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Skeletal Muscle TNF-alpha transcript expression by RT-PCR [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Muscle Inflammatory Infiltrates by Immunohistochemistry [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Oral Glucose tolerance Test [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Insulin Sensitivity by Hyperglycemic Clamp Test [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Bilateral Single Limb Strength Testing (Leg Extension and Leg Press) [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Timed Walks (10 meter and 6 minute walk tests [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Balance Testing using Berg Balance Scale [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  
• Peak Fitness by graded treadmill VO2 peak testing [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
  

This study investigates the hypothesis that a novel, high intensity, high repetition ST program will improve abnormalities in paretic and non-paretic leg muscle volume and composition compared to an attention-matched control regimen of supervised stretching over a 3-month intervention period in those disabled by stroke. We further hypothesize that ST-induced skeletal muscle adaptation will translate into improved insulin sensitivity, strength, and function in this population. The specific objectives are to: 1) Determine the effects ST compared to a control intervention on paretic and non-paretic abnormalities in skeletal muscle volume, intramuscular fat, muscle fiber distribution, muscle capillary density, and muscle inflammation in chronically disabled stroke survivors. 2) Determine the effects ST compared to a control intervention on insulin sensitivity in stroke survivors, and whether structural and cellular skeletal muscle mechanisms contribute to improvements in insulin sensitivity after ST. 3) Determine the effects ST compared to a control intervention on physical function (strength, walking speed and balance) in stroke survivors, and whether structural skeletal muscle mechanisms predict ST-induced functional improvement.

The project design consists of 4 phases over 5 months for stroke participants enrolled in either of the two intervention arms (ST vs. CONTROL). During phase 1 we will screen and consent chronic stroke patients with residual gait deficits. Phase 2 (3 weeks) will consist of baseline testing that includes DEXA scanning, bilateral CT scanning of the legs, bilateral vastus lateralis muscle biopsies, strength testing, timed walks, balance measurements, oral glucose tolerance testing, and hyperglycemic clamp testing. Following completion of baseline testing, volunteers are to be randomized to ST or the CONTROL group. Phase 3 (Intervention Phase, 3 months) will begin with 2 sessions of acclimatization for those assigned to the ST group. ST will then be progressed to 2 sets of 20 repetitions on each leg on each machine (Keiser Leg Press, Leg Extension, Leg Curl) with gradual increases in resistance over 3 months. Those in the CONTROL group will receive equal exposure to health care personnel in the Baltimore VA Exercise facility, performing a full battery of upper and lower body passive and active stretching exercises at each intervention session. In Phase 4 all baseline testing and laboratory analyses will be repeated.

Developing evidence-based therapies to combat skeletal muscle deterioration is highly relevant for chronically disabled stoke survivors. There is mounting evidence that current models of post-stroke rehabilitation are not optimal for maximizing recovery of muscle mass, strength, and metabolic health. The proposed research will develop new insight into the utility of progressive ST for reversing detrimental changes to gross muscle composition, muscle molecular phenotype, muscle inflammation, and muscle capillarization. Changes to any or all of these muscle parameters should have measurable impact on both whole body insulin sensitivity and function.

Collectively, the results from this trial may change the current standard of care for stroke survivors by providing evidenced reasons for augmenting physical therapists' treatments, allowing more intense and diverse therapy sessions for maintenance of skeletal muscle.